Crystal structure of a hepatitis delta virus ribozyme

Area of Science:

• Biochemistry
• Structural Biology
• Virology

Background:

• The hepatitis delta virus (HDV) ribozyme is essential for the pathogen's survival.
• It is the only known catalytic RNA vital for a human pathogen's viability.

Purpose of the Study:

• To determine the high-resolution crystal structure of the self-cleaving genomic HDV ribozyme.
• To elucidate the structural basis of its catalytic activity.

Main Methods:

• Crystallization of a 72-nucleotide self-cleaved HDV ribozyme engineered for protein binding.
• X-ray diffraction to 2.3 A resolution.

Main Results:

• The crystal structure reveals a compact catalytic core with five helical segments in a nested double pseudoknot.
• The active site, containing the 5'-hydroxyl leaving group, is a cleft formed by juxtaposed helices and strand-crossovers.
• The active site's organization resembles that of protein enzymes, with key functional groups surrounding the leaving group.

Conclusions:

• The HDV ribozyme possesses a complex, intricate catalytic core structure.
• Its active site architecture is remarkably similar to protein enzymes, offering insights into RNA catalysis.